Sensitivity and frequencies of dystrophin gene mutations in Thai DMD/BMD patients as detected by multiplex PCR.
BACKGROUND
Duchenne muscular dystrophy (DMD), a lethal X-linked disease affecting 1 in 3500 male births, and its more benign variant, Becker muscular dystrophy (BMD), are caused by mutations in the dystrophin gene. Because of its large size, analysing the whole gene is impractical. Methods have been developed to detect the commonest mutations i.e. the deletions of the exons. Although these tests are highly specific, their sensitivity is inherently limited by the prevalence of deletions, which differs among different populations.


METHODS
We reviewed our database for the detection of Dystrophin gene mutation by means of 31-exon multiplex PCR in Thai males, diagnosed clinically and biochemically with DMD or BMD from July 1994 to November 2006. One index patient was chosen from each family for statistical analysis. The overall sensitivity of the test, the number of fragment deleted, and the deletion frequency of each fragment were calculated, along with their 95% confidence intervals (C.I.).


RESULTS
We found deletions in 99 out of the 202 index patients (49%; Bayesian 95% C.I.=42%-56%). 51% of these had deletion in only one of the 31 exons tested, while the patient with the most extensive deletions had 14 exons deleted. The mean number of deleted exons were 2.84 (BC(a) bootstrap 95% C.I.=2.37-3.48), or 5.02 (3.81-6.85) if all the untested exons adjacent to the confirmed deleted exons were assumed to be deleted. The region spanning exons 44-52 was the most frequently deleted. These were similar to those reported in the Japanese.


CONCLUSIONS
The multiplex PCR detected deletions only in about half of the Thai patients. The diseases therefore should not be excluded solely on the negative result if DMD/BMD is strongly suspected.
Sura
Thanyachai
T
Division of Medical Genetics & Molecular Medicine and Academic Center for Medical Genetics, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Eu-ahsunthornwattana
Jakris
J
Pingsuthiwong
Sarinee
S
Busabaratana
Manisa
M
D003937:Diagnosis, Differential; D016189:Dystrophin / Q000235:genetics*; D006801:Humans; D008297:Male; D020388:Muscular Dystrophy, Duchenne / Q000175:diagnosis / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods*; D011379:Prognosis; D012680:Sensitivity and Specificity
C484258:DMD protein, human; D016189:Dystrophin